NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia.

Autor:	Thomé CH; Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Ferreira GA; Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Pereira-Martins DA; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Dos Santos GA; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Ortiz CA; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., de Souza LEB; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Sobral LM; Department of Clinical Analyses, Toxicology and Food Sciences, University of São Paulo, Ribeirão Preto, Brazil., Silva CLA; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Scheucher PS; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Gil CD; Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil., Leopoldino AM; Department of Clinical Analyses, Toxicology and Food Sciences, University of São Paulo, Ribeirão Preto, Brazil., Silveira DRA; Hematology, Medical School, University of São Paulo, São Paulo, Brazil., Coelho-Silva JL; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Traina F; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Koury LC; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Melo RAM; Department of Internal Medicine, University of Pernambuco, Recife, Brazil., Bittencourt R; Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Pagnano K; Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil., Pasquini R; Hematology Division, Federal University of Paraná, Curitiba, Brazil., Nunes EC; Hematology Division, Federal University of Paraná, Curitiba, Brazil., Fagundes EM; Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil., Gloria ABF; Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil., Kerbauy FR; Federal University of São Paulo, São Paulo, Brazil., Chauffaille ML; Federal University of São Paulo, São Paulo, Brazil., Keating A; Cell Therapy Program, Princess Margaret Cancer Centre, Toronto, Canada., Tallman MS; Leukemia Service, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York, USA., Ribeiro RC; Department of Oncology, St. Jude Children's Research Hospital, Memphis, USA., Dillon R; Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK., Ganser A; Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Löwenberg B; Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands., Valk P; Santa Lucia Foundation, Rome, Italy., Lo-Coco F; Department of Biopathology, Tor Vergata University, Rome, Italy.; Santa Lucia Foundation, Rome, Italy., Sanz MA; Department of Hematology, Valencia University Medical School, Valencia, Spain.; CIBERONC, Instituto Carlos III, Madrid, Spain., Berliner N; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA., Faça VM; Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil., Rego EM; Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil. eduardo.rego@fm.usp.br.; LIM31, Hematology, Medical School, University of São Paulo, São Paulo, Brazil. eduardo.rego@fm.usp.br.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2020 Jun 25; Vol. 10 (1), pp. 10315. Date of Electronic Publication: 2020 Jun 25.
DOI:	10.1038/s41598-020-66223-2
Abstrakt:	Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.
Databáze:	MEDLINE
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